1. Field of the Invention
The present invention relates to novel crystalline oxalate salts of a diamide compound. This invention also relates to pharmaceutical compositions containing such crystalline salts; processes and intermediates useful for preparing such crystalline salts; and methods of using such crystalline salts to, for example, treat a pulmonary disorder.
2. State of the Art
U.S. Patent Application Publication No. US 2010/0273755 A1, published on Oct. 28, 2010, discloses diamide compounds that are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) and asthma. One compound disclosed in this application is biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-methyl}phenylcarbamoyl)butyl]methylcarbamoyl}-ethyl)piperidin-4-yl ester, which has the chemical structure represented by formula I:

Therapeutic agents used for treating pulmonary disorders are typically administered directly into the respiratory tract using an inhalation device, such as a dry powder inhaler (DPI), a metered-dose inhaler (MDI) or a nebulizer inhaler. When formulating a therapeutic agent for use in such devices, it is advantageous to have a stable crystalline form of the therapeutic agent that can be micronized or otherwise formulated and stored without significant decomposition or loss of crystallinity. In particular, the crystalline form should not be excessively hygroscopic or deliquescent. Additionally, the crystalline form should have a relatively high melting point (i.e. greater than about 130° C.) to minimize thermal degradation during processing and storage.
However, the formation of crystalline forms of organic compounds is highly unpredictable. No reliable methods exist for predicting which, if any, form of an organic compound will be crystalline. Moreover, no methods exist for predicting which, if any, crystalline form will have the physically properties desired for use in, e.g., pharmaceutical inhalation devices.
At present, no crystalline form of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-phenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl ester has been disclosed. Accordingly, a need exists for a stable crystalline form of this compound. In particular, a need exists for a stable, non-deliquescent crystalline form which has an acceptable level of hygroscopicity and a relatively high melting point.